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Depression is more than the sum score of its parts: individual DSM symptoms have different risk factors

  • E. I. Fried (a1) (a2), R. M. Nesse (a3) (a4), K. Zivin (a4) (a5) (a6), C. Guille (a7) and S. Sen (a4)...



For diagnostic purposes, the nine symptoms that compose the DSM-5 criteria for major depressive disorder (MDD) are assumed to be interchangeable indicators of one underlying disorder, implying that they should all have similar risk factors. The present study investigates this hypothesis, using a population cohort that shifts from low to elevated depression levels.


We assessed the nine DSM-5 MDD criterion symptoms (using the Patient Health Questionnaire; PHQ-9) and seven depression risk factors (personal and family MDD history, sex, childhood stress, neuroticism, work hours, and stressful life events) in a longitudinal study of medical interns prior to and throughout internship (n = 1289). We tested whether risk factors varied across symptoms, and whether a latent disease model could account for heterogeneity between symptoms.


All MDD symptoms increased significantly during residency training. Four risk factors predicted increases in unique subsets of PHQ-9 symptoms over time (depression history, childhood stress, sex, and stressful life events), whereas neuroticism and work hours predicted increases in all symptoms, albeit to varying magnitudes. MDD family history did not predict increases in any symptom. The strong heterogeneity of associations persisted after controlling for a latent depression factor.


The influence of risk factors varies substantially across DSM depression criterion symptoms. As symptoms are etiologically heterogeneous, considering individual symptoms in addition to depression diagnosis might offer important insights obfuscated by symptom sum scores.


Corresponding author

* Address for correspondence: Dr S. Sen, Rachel Upjohn Building, 4250 Plymouth Rd, Ann Arbor, MI 48109-5734, USA. (Email:


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